A work led by SISSA [Scuola Internazionale Superiore di Studi Avanzati] and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of ion ‘trapping’ by graphene carpets and its effect on the communication between neurons. The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition. Graphene is the thinnest bi-dimensional material available today, characterised by incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.

A study conducted by SISSA – Scuola Internazionale Superiore di Studi Avanzati, in association with the University of Antwerp (Belgium), the University of Trieste and the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now. “It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped. It is this small variation that determines the increase in neuronal excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.

The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices”.

It is a study with a double outcome. Laura Ballerini comments as follows: “This ‘ion trap’ effect was described only in theory. Studying the impact of the ‘technology of materials’ on biological systems, we have documented a mechanism to regulate membrane excitability, but at the same time we have also experimentally described a property of the material through the biology of neurons.”

Dexter Johnson in a June 13, 2018 posting, on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website), provides more context for the work (Note: Links have been removed),

While graphene has been tapped to deliver on everything from electronics to optoelectronics, it’s a bit harder to picture how it may offer a key tool for addressing neurological damage and disorders. But that’s exactly what researchers have been looking at lately because of the wonder material’s conductivity and transparency.

In the most recent development, a team from Europe has offered a deeper understanding of how graphene can be combined with neurological tissue and, in so doing, may have not only given us an additional tool for neurological medicine, but also provided a tool for gaining insights into other biological processes.

“The results demonstrate that, depending on how the interface with [single-layer graphene] is engineered, the material may tune neuronal activities by altering the ion mobility, in particular potassium, at the cell/substrate interface,” said Laura Ballerini, a researcher in neurons and nanomaterials at SISSA.

Ballerini provided some context for this most recent development by explaining that graphene-based nanomaterials have come to represent potential tools in neurology and neurosurgery.

“These materials are increasingly engineered as components of a variety of applications such as biosensors, interfaces, or drug-delivery platforms,” said Ballerini. “In particular, in neural electrode or interfaces, a precise requirement is the stable device/neuronal electrical coupling, which requires governing the interactions between the electrode surface and the cell membrane.”

This neuro-electrode hybrid is at the core of numerous studies, she explained, and graphene, thanks to its electrical properties, transparency, and flexibility represents an ideal material candidate.

In all of this work, the real challenge has been to investigate the ability of a single atomic layer to tune neuronal excitability and to demonstrate unequivocally that graphene selectively modifies membrane-associated neuronal functions.

…

I encourage you to read Dexter’s posting as it clarifies the work described in the SISSA press release for those of us (me) who may fail to grasp the implications.

All this brings to mind a prediction made about the Graphene Flagship and the Human Brain Project shortly after the European Commission announced in January 2013 that each project had won funding of 1B Euros to be paid out over a period of 10 years. The prediction was that scientists would work on graphene/human brain research.

This is not the first time I’ve posted about nanotechnology and neuroscience (see this April 2, 2013 piece about then new brain science initiative in the US and Michael Berger’s Nanowerk Spotlight article/review of an earlier paper covering the topic of nanotechnology and neuroscience).

Interestingly, the European Union (EU) had announced its two $1B Euro research initiatives, the Human Brain Project and the Graphene Flagship (see my Jan. 28, 2013 posting about it), months prior to the US brain research push. For those unfamiliar with the nanotechnology effort, graphene is a nanomaterial and there is high interest in its potential use in biomedical technology, thus partially connecting both EU projects.

In any event, Berger is highlighting a nanotechnology and neuroscience connection again in his Oct. 18, 2017 Nanowerk Spotlight article, or overview of, a new paper, which updates our understanding of the potential connections between the two fields (Note: A link has been removed),

…

Over the past several years, nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience and brain activity mapping.

A review paper in Advanced Functional Materials (“Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping”) summarizes the basic concepts associated with neuroscience and the current journey of nanotechnology towards the study of neuron function by addressing various concerns on the significant role of nanomaterials in neuroscience and by describing the future applications of this emerging technology.

…

The collaboration between nanotechnology and neuroscience, though still at the early stages, utilizes broad concepts, such as drug delivery, cell protection, cell regeneration and differentiation, imaging and surgery, to give birth to novel clinical methods in neuroscience.

…

Ultimately, the clinical translation of nanoneuroscience implicates that central nervous system (CNS) diseases, including neurodevelopmental, neurodegenerative and psychiatric diseases, have the potential to be cured, while the industrial translation of nanoneuroscience indicates the need for advancement of brain-computer interface technologies.

…

Future Developing Arenas in Nanoneuroscience

The Brain Activity Map (BAM) Project aims to map the neural activity of every neuron across all neural circuits with the ultimate aim of curing diseases associated with the nervous system. The announcement of this collaborative, public-private research initiative in 2013 by President Obama has driven the surge in developing methods to elucidate neural circuitry. Three current developing arenas in the context of nanoneuroscience applications that will push such initiative forward are 1) optogenetics, 2) molecular/ion sensing and monitoring and 3) piezoelectric effects.

In their review, the authors discuss these aspects in detail.

Neurotoxicity of Nanomaterials

By engineering particles on the scale of molecular-level entities – proteins, lipid bilayers and nucleic acids – we can stereotactically interface with many of the components of cell systems, and at the cutting edge of this technology, we can begin to devise ways in which we can manipulate these components to our own ends. However, interfering with the internal environment of cells, especially neurons, is by no means simple.

“If we are to continue to make great strides in nanoneuroscience, functional investigations of nanomaterials must be complemented with robust toxicology studies,” the authors point out. “A database on the toxicity of materials that fully incorporates these findings for use in future schema must be developed. These databases should include information and data on 1) the chemical nature of the nanomaterials in complex aqueous environments; 2) the biological interactions of nanomaterials with chemical specificity; 3) the effects of various nanomaterial properties on living systems; and 4) a model for the simulation and computation of possible effects of nanomaterials in living systems across varying time and space. If we can establish such methods, it may be possible to design nanopharmaceuticals for improved research as well as quality of life.”

…

“However, challenges in nanoneuroscience are present in many forms, such as neurotoxicity; the inability to cross the blood-brain barrier [emphasis mine]; the need for greater specificity, bioavailability and short half-lives; and monitoring of disease treatment,” the authors conclude their review. “The nanoneurotoxicity surrounding these nanomaterials is a barrier that must be overcome for the translation of these applications from bench-to-bedside. While the challenges associated with nanoneuroscience seem unending, they represent opportunities for future work.”

…

I have a March 26, 2015 posting about Canadian researchers breaching the blood-brain barrier and an April 13, 2016 posting about US researchers at Cornell University also breaching the blood-brain barrier. Perhaps the “inability” mentioned in this Spotlight article means that it can’t be done consistently or that it hasn’t been achieved on humans.

I have two news bits (dated almost one month apart) about the use of graphene in neural probes, one from the European Union and the other from Korea.

European Union (EU)

This work is being announced by the European Commission’s (a subset of the EU) Graphene Flagship (one of two mega-funding projects announced in 2013; 1B Euros each over ten years for the Graphene Flagship and the Human Brain Project).

According to a March 27, 2017 news item on ScienceDaily, researchers have developed a graphene-based neural probe that has been tested on rats,

Measuring brain activity with precision is essential to developing further understanding of diseases such as epilepsy and disorders that affect brain function and motor control. Neural probes with high spatial resolution are needed for both recording and stimulating specific functional areas of the brain. Now, researchers from the Graphene Flagship have developed a new device for recording brain activity in high resolution while maintaining excellent signal to noise ratio (SNR). Based on graphene field-effect transistors, the flexible devices open up new possibilities for the development of functional implants and interfaces.

The research, published in 2D Materials, was a collaborative effort involving Flagship partners Technical University of Munich (TU Munich; Germany), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; Spain), Spanish National Research Council (CSIC; Spain), The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN; Spain) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2; Spain).

Caption: Graphene transistors integrated in a flexible neural probe enables electrical signals from neurons to be measured with high accuracy and density. Inset: The tip of the probe contains 16 flexible graphene transistors. Credit: ICN2

The devices were used to record the large signals generated by pre-epileptic activity in rats, as well as the smaller levels of brain activity during sleep and in response to visual light stimulation. These types of activities lead to much smaller electrical signals, and are at the level of typical brain activity. Neural activity is detected through the highly localised electric fields generated when neurons fire, so densely packed, ultra-small measuring devices is important for accurate brain readings.

The neural probes are placed directly on the surface of the brain, so safety is of paramount importance for the development of graphene-based neural implant devices. Importantly, the researchers determined that the graphene-based probes are non-toxic, and did not induce any significant inflammation.

Devices implanted in the brain as neural prosthesis for therapeutic brain stimulation technologies and interfaces for sensory and motor devices, such as artificial limbs, are an important goal for improving quality of life for patients. This work represents a first step towards the use of graphene in research as well as clinical neural devices, showing that graphene-based technologies can deliver the high resolution and high SNR needed for these applications.

First author Benno Blaschke (TU Munich) said “Graphene is one of the few materials that allows recording in a transistor configuration and simultaneously complies with all other requirements for neural probes such as flexibility, biocompability and chemical stability. Although graphene is ideally suited for flexible electronics, it was a great challenge to transfer our fabrication process from rigid substrates to flexible ones. The next step is to optimize the wafer-scale fabrication process and improve device flexibility and stability.”

Jose Antonio Garrido (ICN2), led the research. He said “Mechanical compliance is an important requirement for safe neural probes and interfaces. Currently, the focus is on ultra-soft materials that can adapt conformally to the brain surface. Graphene neural interfaces have shown already great potential, but we have to improve on the yield and homogeneity of the device production in order to advance towards a real technology. Once we have demonstrated the proof of concept in animal studies, the next goal will be to work towards the first human clinical trial with graphene devices during intraoperative mapping of the brain. This means addressing all regulatory issues associated to medical devices such as safety, biocompatibility, etc.”

Caption: The graphene-based neural probes were used to detect rats’ responses to visual stimulation, as well as neural signals during sleep. Both types of signals are small, and typically difficult to measure. Credit: ICN2

While this research from Korea was published more recently, the probe itself has not been subjected to in vivo (animal testing). From an April 19, 2017 news item on ScienceDaily,

Electrodes placed in the brain record neural activity, and can help treat neural diseases like Parkinson’s and epilepsy. Interest is also growing in developing better brain-machine interfaces, in which electrodes can help control prosthetic limbs. Progress in these fields is hindered by limitations in electrodes, which are relatively stiff and can damage soft brain tissue.

Designing smaller, gentler electrodes that still pick up brain signals is a challenge because brain signals are so weak. Typically, the smaller the electrode, the harder it is to detect a signal. However, a team from the Daegu Gyeongbuk Institute of Science & Technology [DGIST} in Korea developed new probes that are small, flexible and read brain signals clearly.

The probe consists of an electrode, which records the brain signal. The signal travels down an interconnection line to a connector, which transfers the signal to machines measuring and analysing the signals.

The electrode starts with a thin gold base. Attached to the base are tiny zinc oxide nanowires, which are coated in a thin layer of gold, and then a layer of conducting polymer called PEDOT. These combined materials increase the probe’s effective surface area, conducting properties, and strength of the electrode, while still maintaining flexibility and compatibility with soft tissue.

Packing several long, thin nanowires together onto one probe enables the scientists to make a smaller electrode that retains the same effective surface area of a larger, flat electrode. This means the electrode can shrink, but not reduce signal detection. The interconnection line is made of a mix of graphene and gold. Graphene is flexible and gold is an excellent conductor. The researchers tested the probe and found it read rat brain signals very clearly, much better than a standard flat, gold electrode.

“Our graphene and nanowires-based flexible electrode array can be useful for monitoring and recording the functions of the nervous system, or to deliver electrical signals to the brain,” the researchers conclude in their paper recently published in the journal ACS Applied Materials and Interfaces.

The probe requires further clinical tests before widespread commercialization. The researchers are also interested in developing a wireless version to make it more convenient for a variety of applications.

There’s been a lot of talk about using graphene-based implants in the brain due to the material’s flexibility along with its other properties. A step forward has been taking according to a Jan. 29, 2016 news item on phys.org,

Researchers have successfully demonstrated how it is possible to interface graphene – a two-dimensional form of carbon – with neurons, or nerve cells, while maintaining the integrity of these vital cells. The work may be used to build graphene-based electrodes that can safely be implanted in the brain, offering promise for the restoration of sensory functions for amputee or paralysed patients, or for individuals with motor disorders such as epilepsy or Parkinson’s disease.

Previously, other groups had shown that it is possible to use treated graphene to interact with neurons. However the signal to noise ratio from this interface was very low. By developing methods of working with untreated graphene, the researchers retained the material’s electrical conductivity, making it a significantly better electrode.

“For the first time we interfaced graphene to neurons directly,” said Professor Laura Ballerini of the University of Trieste in Italy. “We then tested the ability of neurons to generate electrical signals known to represent brain activities, and found that the neurons retained their neuronal signalling properties unaltered. This is the first functional study of neuronal synaptic activity using uncoated graphene based materials.”

Our understanding of the brain has increased to such a degree that by interfacing directly between the brain and the outside world we can now harness and control some of its functions. For instance, by measuring the brain’s electrical impulses, sensory functions can be recovered. This can be used to control robotic arms for amputee patients or any number of basic processes for paralysed patients – from speech to movement of objects in the world around them. Alternatively, by interfering with these electrical impulses, motor disorders (such as epilepsy or Parkinson’s) can start to be controlled.

Scientists have made this possible by developing electrodes that can be placed deep within the brain. These electrodes connect directly to neurons and transmit their electrical signals away from the body, allowing their meaning to be decoded.

However, the interface between neurons and electrodes has often been problematic: not only do the electrodes need to be highly sensitive to electrical impulses, but they need to be stable in the body without altering the tissue they measure.

Too often the modern electrodes used for this interface (based on tungsten or silicon) suffer from partial or complete loss of signal over time. This is often caused by the formation of scar tissue from the electrode insertion, which prevents the electrode from moving with the natural movements of the brain due to its rigid nature.

Graphene has been shown to be a promising material to solve these problems, because of its excellent conductivity, flexibility, biocompatibility and stability within the body.

Based on experiments conducted in rat brain cell cultures, the researchers found that untreated graphene electrodes interfaced well with neurons. By studying the neurons with electron microscopy and immunofluorescence the researchers found that they remained healthy, transmitting normal electric impulses and, importantly, none of the adverse reactions which lead to the damaging scar tissue were seen.

According to the researchers, this is the first step towards using pristine graphene-based materials as an electrode for a neuro-interface. In future, the researchers will investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons, and whether tuning the material properties of graphene might alter the synapses and neuronal excitability in new and unique ways. “Hopefully this will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer unwanted side effects,” said Ballerini.

“We are currently involved in frontline research in graphene technology towards biomedical applications,” said Professor Maurizio Prato from the University of Trieste. “In this scenario, the development and translation in neurology of graphene-based high-performance biodevices requires the exploration of the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is only a first step in that direction.”

“These initial results show how we are just at the tip of the iceberg when it comes to the potential of graphene and related materials in bio-applications and medicine,” said Professor Andrea Ferrari, Director of the Cambridge Graphene Centre. “The expertise developed at the Cambridge Graphene Centre allows us to produce large quantities of pristine material in solution, and this study proves the compatibility of our process with neuro-interfaces.”

The research was funded by the Graphene Flagship [emphasis mine], a European initiative which promotes a collaborative approach to research with an aim of helping to translate graphene out of the academic laboratory, through local industry and into society.

There are a couple things I found a bit odd about this project. First, all of the funding is from the Graphene Flagship initiative. I was expecting to see at least some funding from the European Union’s other mega-sized science initiative, the Human Brain Project. Second, there was no mention of Spain nor were there any quotes from the Spanish researchers. For the record, the Spanish institutions represented were: University of Castilla-La Mancha, Carbon Nanobiotechnology Laboratory, and the Basque Foundation for Science.

If you want to learn how something works, one strategy is to take it apart and put it back together again [also known as reverse engineering]. For 10 years, a global initiative called the Blue Brain Project–hosted at the Ecole Polytechnique Federale de Lausanne (EPFL)–has been attempting to do this digitally with a section of juvenile rat brain. The project presents a first draft of this reconstruction, which contains over 31,000 neurons, 55 layers of cells, and 207 different neuron subtypes, on October 8 [2015] in Cell.

Heroic efforts are currently being made to define all the different types of neurons in the brain, to measure their electrical firing properties, and to map out the circuits that connect them to one another. These painstaking efforts are giving us a glimpse into the building blocks and logic of brain wiring. However, getting a full, high-resolution picture of all the features and activity of the neurons within a brain region and the circuit-level behaviors of these neurons is a major challenge.

Henry Markram and colleagues have taken an engineering approach to this question by digitally reconstructing a slice of the neocortex, an area of the brain that has benefitted from extensive characterization. Using this wealth of data, they built a virtual brain slice representing the different neuron types present in this region and the key features controlling their firing and, most notably, modeling their connectivity, including nearly 40 million synapses and 2,000 connections between each brain cell type.

“The reconstruction required an enormous number of experiments,” says Markram, of the EPFL. “It paves the way for predicting the location, numbers, and even the amount of ion currents flowing through all 40 million synapses.”

Once the reconstruction was complete, the investigators used powerful supercomputers to simulate the behavior of neurons under different conditions. Remarkably, the researchers found that, by slightly adjusting just one parameter, the level of calcium ions, they could produce broader patterns of circuit-level activity that could not be predicted based on features of the individual neurons. For instance, slow synchronous waves of neuronal activity, which have been observed in the brain during sleep, were triggered in their simulations, suggesting that neural circuits may be able to switch into different “states” that could underlie important behaviors.

“An analogy would be a computer processor that can reconfigure to focus on certain tasks,” Markram says. “The experiments suggest the existence of a spectrum of states, so this raises new types of questions, such as ‘what if you’re stuck in the wrong state?'” For instance, Markram suggests that the findings may open up new avenues for explaining how initiating the fight-or-flight response through the adrenocorticotropic hormone yields tunnel vision and aggression.

The Blue Brain Project researchers plan to continue exploring the state-dependent computational theory while improving the model they’ve built. All of the results to date are now freely available to the scientific community at https://bbp.epfl.ch/nmc-portal.

Published by the renowned journal Cell, the paper is the result of a massive effort by 82 scientists and engineers at EPFL and at institutions in Israel, Spain, Hungary, USA, China, Sweden, and the UK. It represents the culmination of 20 years of biological experimentation that generated the core dataset, and 10 years of computational science work that developed the algorithms and built the software ecosystem required to digitally reconstruct and simulate the tissue.

The Hebrew University of Jerusalem’s Prof. Idan Segev, a senior author of the research paper, said: “With the Blue Brain Project, we are creating a digital reconstruction of the brain and using supercomputer simulations of its electrical behavior to reveal a variety of brain states. This allows us to examine brain phenomena within a purely digital environment and conduct experiments previously only possible using biological tissue. The insights we gather from these experiments will help us to understand normal and abnormal brain states, and in the future may have the potential to help us develop new avenues for treating brain disorders.”

Segev, a member of the Hebrew University’s Edmond and Lily Safra Center for Brain Sciences and director of the university’s Department of Neurobiology, sees the paper as building on the pioneering work of the Spanish anatomist Ramon y Cajal from more than 100 years ago: “Ramon y Cajal began drawing every type of neuron in the brain by hand. He even drew in arrows to describe how he thought the information was flowing from one neuron to the next. Today, we are doing what Cajal would be doing with the tools of the day: building a digital representation of the neurons and synapses, and simulating the flow of information between neurons on supercomputers. Furthermore, the digitization of the tissue is open to the community and allows the data and the models to be preserved and reused for future generations.”

While a long way from digitizing the whole brain, the study demonstrates that it is feasible to digitally reconstruct and simulate brain tissue, and most importantly, to reveal novel insights into the brain’s functioning. Simulating the emergent electrical behavior of this virtual tissue on supercomputers reproduced a range of previous observations made in experiments on the brain, validating its biological accuracy and providing new insights into the functioning of the neocortex. This is a first step and a significant contribution to Europe’s Human Brain Project, which Henry Markram founded, and where EPFL is the coordinating partner.

Cell has made a video abstract available (it can be found with the Hebrew University of Jerusalem press release)

My most substantive description of the Blue Brain Project , previous to this, was in a Jan. 29, 2013 posting featuring the European Union’s (EU) Human Brain project and involvement from countries that are not members.

* I edited a redundant lede (That’s a virtual slice of a rat brain.), moved the second sentence to the lede while adding this: *about this virtual brain slice* on Oct. 16, 2015 at 0955 hours PST.

A graphene-based artificial retina project has managed to intermingle the European Union’s two major FET (Future and Emerging Technologies) funding projects, 1B Euros each to be disbursed over 10 years, the Graphene Flagship and the Human Brain Project. From an Aug. 7, 2014 Technische Universitaet Muenchen (TUM) news release (also on EurekAlert),

Because of its unusual properties, graphene holds great potential for applications, especially in the field of medical technology. A team of researchers led by Dr. Jose A. Garrido at the Walter Schottky Institut of the TUM is taking advantage of these properties. In collaboration with partners from the Institut de la Vision of the Université Pierre et Marie Curie in Paris and the French company Pixium Vision, the physicists are developing key components of an artificial retina made of graphene.

Retina implants can serve as optical prostheses for blind people whose optical nerves are still intact. The implants convert incident light into electrical impulses that are transmitted to the brain via the optical nerve. There, the information is transformed into images. Although various approaches for implants exist today, the devices are often rejected by the body and the signals transmitted to the brain are generally not optimal.

Already funded by the Human Brain Project as part of the Neurobotics effort, Garrido and his colleagues will now also receive funding from the Graphene Flagship. As of July 2014, the Graphene Flagship has added 86 new partners including TUM according to the news release.

Here’s an image of an ‘invisible’ graphene sensor (a precursor to developing an artificial retina),

Graphene electronics can be prepared on flexible substrates. Only the gold metal leads are visible in the transparent graphene sensor. (Photo: Natalia Hutanu / TUM)

Artificial retinas were first featured on this blog in an Aug. 18, 2011 posting about video game Deus Ex: Human Revolution which features a human character with artificial sight. The post includes links to a video of a scientist describing an artificial retina trial with 30 people and an Israeli start-up company, ‘Nano Retina’, along with information about ‘Eyeborg’, a Canadian filmmaker who on losing an eye in an accident had a camera implanted in the previously occupied eye socket.

More recently, a Feb. 15, 2013 posting featured news about the US Food and Drug Administration’s decision to allow sale of the first commercial artificial retinas in the US in the context of news about a neuroprosthetic implant in a rat which allowed it to see in the infrared range, normally an impossible feat.

The Brain research, ethics, and nanotechnology (part one of five) May 19, 2014 post kicked off a series titled ‘Brains, prostheses, nanotechnology, and human enhancement’ which brings together a number of developments in the worlds of neuroscience*, prosthetics, and, incidentally, nanotechnology in the field of interest called human enhancement. Parts one through four are an attempt to draw together a number of new developments, mostly in the US and in Europe. Due to my language skills which extend to English and, more tenuously, French, I can’t provide a more ‘global perspective’. Part five features a summary.

Before further discussing the US Presidential Commission for the Study of Bioethical Issues ‘brain’ meetings mentioned in part one, I have some background information.

The US launched its self-explanatory BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative (originally called BAM; Brain Activity Map) in 2013. (You can find more about the history and details in this Wikipedia entry.)

From the beginning there has been discussion about how nanotechnology will be of fundamental use in the US BRAIN initiative and the European Union’s 10 year Human Brain Project (there’s more about that in my Jan. 28, 2013 posting). There’s also a 2013 book (Nanotechnology, the Brain, and the Future) from Springer, which, according to the table of contents, presents an exciting (to me) range of ideas about nanotechnology and brain research,

I. Introduction and key resources

1. Nanotechnology, the brain, and the future: Anticipatory governance via end-to-end real-time technology assessment by Jason Scott Robert, Ira Bennett, and Clark A. Miller
2. The complex cognitive systems manifesto by Richard P. W. Loosemore
3. Analysis of bibliometric data for research at the intersection of nanotechnology and neuroscience by Christina Nulle, Clark A. Miller, Harmeet Singh, and Alan Porter
4. Public attitudes toward nanotechnology-enabled human enhancement in the United States by Sean Hays, Michael Cobb, and Clark A. Miller
5. U.S. news coverage of neuroscience nanotechnology: How U.S. newspapers have covered neuroscience nanotechnology during the last decade by Doo-Hun Choi, Anthony Dudo, and Dietram Scheufele
6. Nanoethics and the brain by Valerye Milleson
7. Nanotechnology and religion: A dialogue by Tobie Milford

II. Brain repair

8. The age of neuroelectronics by Adam Keiper
9. Cochlear implants and Deaf culture by Derrick Anderson
10. Healing the blind: Attitudes of blind people toward technologies to cure blindness by Arielle Silverman
11. Ethical, legal and social aspects of brain-implants using nano-scale materials and techniques by Francois Berger et al.
12. Nanotechnology, the brain, and personal identity by Stephanie Naufel

III. Brain enhancement

13. Narratives of intelligence: the sociotechnical context of cognitive enhancement by Sean Hays
14. Towards responsible use of cognitive-enhancing drugs by the healthy by Henry T. Greeley et al.
15. The opposite of human enhancement: Nanotechnology and the blind chicken debate by Paul B. Thompson
16. Anticipatory governance of human enhancement: The National Citizens’ Technology Forum by Patrick Hamlett, Michael Cobb, and David Guston
a. Arizona site report
b. California site report
c. Colorado site reportd. Georgia site report
e. New Hampshire site report
f. Wisconsin site report

IV. Brain damage

17. A review of nanoparticle functionality and toxicity on the central nervous system by Yang et al.
18. Recommendations for a municipal health and safety policy for nanomaterials: A Report to the City of Cambridge City Manager by Sam Lipson
19. Museum of Science Nanotechnology Forum lets participants be the judge by Mark Griffin
20. Nanotechnology policy and citizen engagement in Cambridge, Massachusetts: Local reflexive governance by Shannon Conley

Thanks to David Bruggeman’s May 13, 2014 posting on his Pasco Phronesis blog, I stumbled across both a future meeting notice and documentation of the Feb. 2014 meeting of the Presidential Commission for the Study of Bioethical Issues (Note: Links have been removed),

Continuing from its last meeting (in February 2014), the Presidential Commission for the Study of Bioethical Issues will continue working on the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in its June 9-10 meeting in Atlanta, Georgia. An agenda is still forthcoming, …

…

In other developments, Commission staff are apparently going to examine some efforts to engage bioethical issues through plays. I’d be very excited to see some of this happen during a Commission meeting, but any little bit is interesting. The authors of these plays, Karen H. Rothenburg and Lynn W. Bush, have published excerpts in their book The Drama of DNA: Narrative Genomics. …

The Commission also has a YouTube channel …

Integrating a theatrical experience into the reams of public engagement exercises that technologies such as stem cell, GMO (genetically modified organisms), nanotechnology, etc. tend to spawn seems a delightful idea.

Interestingly, the meeting in June 2014 will coincide with the book’s release date. I dug further and found these snippets of information. The book is being published by Oxford University Press and is available in both paperback and e-book formats. The authors are not playwrights, as one might assume. From the Author Information page,

Lynn Bush, PhD, MS, MA is on the faculty of Pediatric Clinical Genetics at Columbia University Medical Center, a faculty associate at their Center for Bioethics, and serves as an ethicist on pediatric and genomic advisory committees for numerous academic medical centers and professional organizations. Dr. Bush has an interdisciplinary graduate background in clinical and developmental psychology, bioethics, genomics, public health, and neuroscience that informs her research, writing, and teaching on the ethical, psychological, and policy challenges of genomic medicine and clinical research with children, and prenatal-newborn screening and sequencing.

Karen H. Rothenberg, JD, MPA serves as Senior Advisor on Genomics and Society to the Director, National Human Genome Research Institute and Visiting Scholar, Department of Bioethics, Clinical Center, National Institutes of Health. She is the Marjorie Cook Professor of Law, Founding Director, Law & Health Care Program and former Dean at the University of Maryland Francis King Carey School of Law and Visiting Professor, Johns Hopkins Berman Institute of Bioethics. Professor Rothenberg has served as Chair of the Maryland Stem Cell Research Commission, President of the American Society of Law, Medicine and Ethics, and has been on many NIH expert committees, including the NIH Recombinant DNA Advisory Committee.

It is possible to get a table of contents for the book but I notice not a single playwright is mentioned in any of the promotional material for the book. While I like the idea in principle, it seems a bit odd and suggests that these are purpose-written plays. I have not had good experiences with purpose-written plays which tend to be didactic and dull, especially when they’re not devised by a professional storyteller.

It turns out, there are some Canadian tidbits. From the Meeting Sixteen: Feb. 10-11, 2014 webcasts page, (each presenter is featured in their own webcast of approximately 11 mins.)

Timothy Caulfield, LL.M., F.R.S.C., F.C.A.H.S.

Canada Research Chair in Health Law and Policy
Professor in the Faculty of Law
and the School of Public Health
University of Alberta

Eric Racine, Ph.D.

Director, Neuroethics Research Unit
Associate Research Professor
Institut de Recherches Cliniques de Montréal
Associate Research Professor,
Department of Medicine
Université de Montréal
Adjunct Professor, Department of Medicine and Department of Neurology and Neurosurgery,
McGill University

It was a surprise to see a couple of Canucks listed as presenters and I’m grateful that the Presidential Commission for the Study of Bioethical Issues is so generous with information. in addition to the webcasts, there is the Federal Register Notice of the meeting, an agenda, transcripts, and presentation materials. By the way, Caulfield discussed hype and Racine discussed public understanding of science with regard to neuroscience both fitting into the overall theme of communication. I’ll have to look more thoroughly but it seems to me there’s no mention of pop culture as a means of communicating about science and technology.

Links to other posts in the Brains, prostheses, nanotechnology, and human enhancement five-part series:

Miguel Nicolelis, a professor at Duke University, has been making international headlines lately with two brain projects. The first one about implanting a brain chip that allows rats to perceive infrared light was mentioned in my Feb. 15, 2013 posting. The latest project is a brain-to-brain (rats) communication project as per a Feb. 28, 2013 news release on *EurekAlert,

Researchers have electronically linked the brains of pairs of rats for the first time, enabling them to communicate directly to solve simple behavioral puzzles. A further test of this work successfully linked the brains of two animals thousands of miles apart—one in Durham, N.C., and one in Natal, Brazil.

The results of these projects suggest the future potential for linking multiple brains to form what the research team is calling an “organic computer,” which could allow sharing of motor and sensory information among groups of animals. The study was published Feb. 28, 2013, in the journal Scientific Reports.

“Our previous studies with brain-machine interfaces had convinced us that the rat brain was much more plastic than we had previously thought,” said Miguel Nicolelis, M.D., PhD, lead author of the publication and professor of neurobiology at Duke University School of Medicine. “In those experiments, the rat brain was able to adapt easily to accept input from devices outside the body and even learn how to process invisible infrared light generated by an artificial sensor. So, the question we asked was, ‘if the brain could assimilate signals from artificial sensors, could it also assimilate information input from sensors from a different body?'”

Ben Schiller in a Mar. 1, 2013 article for Fast Company describes both the latest experiment and the work leading up to it,

First, two rats were trained to press a lever when a light went on in their cage. Press the right lever, and they would get a reward–a sip of water. The animals were then split in two: one cage had a lever with a light, while another had a lever without a light. When the first rat pressed the lever, the researchers sent electrical activity from its brain to the second rat. It pressed the right lever 70% of the time (more than half).

In another experiment, the rats seemed to collaborate. When the second rat didn’t push the right lever, the first rat was denied a drink. That seemed to encourage the first to improve its signals, raising the second rat’s lever-pushing success rate.

Finally, to show that brain-communication would work at a distance, the researchers put one rat in an cage in North Carolina, and another in Natal, Brazil. Despite noise on the Internet connection, the brain-link worked just as well–the rate at which the second rat pushed the lever was similar to the experiment conducted solely in the U.S.

To test this hypothesis, the researchers first trained pairs of rats to solve a simple problem: to press the correct lever when an indicator light above the lever switched on, which rewarded the rats with a sip of water. They next connected the two animals’ brains via arrays of microelectrodes inserted into the area of the cortex that processes motor information.

One of the two rodents was designated as the “encoder” animal. This animal received a visual cue that showed it which lever to press in exchange for a water reward. Once this “encoder” rat pressed the right lever, a sample of its brain activity that coded its behavioral decision was translated into a pattern of electrical stimulation that was delivered directly into the brain of the second rat, known as the “decoder” animal.

The decoder rat had the same types of levers in its chamber, but it did not receive any visual cue indicating which lever it should press to obtain a reward. Therefore, to press the correct lever and receive the reward it craved, the decoder rat would have to rely on the cue transmitted from the encoder via the brain-to-brain interface.

The researchers then conducted trials to determine how well the decoder animal could decipher the brain input from the encoder rat to choose the correct lever. The decoder rat ultimately achieved a maximum success rate of about 70 percent, only slightly below the possible maximum success rate of 78 percent that the researchers had theorized was achievable based on success rates of sending signals directly to the decoder rat’s brain.

Importantly, the communication provided by this brain-to-brain interface was two-way. For instance, the encoder rat did not receive a full reward if the decoder rat made a wrong choice. The result of this peculiar contingency, said Nicolelis, led to the establishment of a “behavioral collaboration” between the pair of rats.

“We saw that when the decoder rat committed an error, the encoder basically changed both its brain function and behavior to make it easier for its partner to get it right,” Nicolelis said. “The encoder improved the signal-to-noise ratio of its brain activity that represented the decision, so the signal became cleaner and easier to detect. And it made a quicker, cleaner decision to choose the correct lever to press. Invariably, when the encoder made those adaptations, the decoder got the right decision more often, so they both got a better reward.”

In a second set of experiments, the researchers trained pairs of rats to distinguish between a narrow or wide opening using their whiskers. If the opening was narrow, they were taught to nose-poke a water port on the left side of the chamber to receive a reward; for a wide opening, they had to poke a port on the right side.

The researchers then divided the rats into encoders and decoders. The decoders were trained to associate stimulation pulses with the left reward poke as the correct choice, and an absence of pulses with the right reward poke as correct. During trials in which the encoder detected the opening width and transmitted the choice to the decoder, the decoder had a success rate of about 65 percent, significantly above chance.

To test the transmission limits of the brain-to-brain communication, the researchers placed an encoder rat in Brazil, at the Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), and transmitted its brain signals over the Internet to a decoder rat in Durham, N.C. They found that the two rats could still work together on the tactile discrimination task.

“So, even though the animals were on different continents, with the resulting noisy transmission and signal delays, they could still communicate,” said Miguel Pais-Vieira, PhD, a postdoctoral fellow and first author of the study. “This tells us that it could be possible to create a workable, network of animal brains distributed in many different locations.”

Will Oremus in his Feb. 28, 2013 article for Slate seems a little less buoyant about the implications of this work,

Nicolelis believes this opens the possibility of building an “organic computer” that links the brains of multiple animals into a single central nervous system, which he calls a “brain-net.” Are you a little creeped out yet? In a statement, Nicolelis adds:

We cannot even predict what kinds of emergent properties would appear when animals begin interacting as part of a brain-net. In theory, you could imagine that a combination of brains could provide solutions that individual brains cannot achieve by themselves.

That sounds far-fetched. But Nicolelis’ lab is developing quite the track record of “taking science fiction and turning it into science,” says Ron Frostig, a neurobiologist at UC-Irvine who was not involved in the rat study. “He’s the most imaginative neuroscientist right now.” (Frostig made it clear he meant this as a complement, though skeptics might interpret the word less charitably.)

While there’s much excitement about Nicolelis and his work, there are other ‘brain’ projects being developed in the US including the Brain Activity Map (BAM), which James Lewis notes in his Mar. 1, 2013 posting on the Foresight Institute blog,

A proposal alluded to by President Obama in his State of the Union address [Feb. 2013] to construct a dynamic “functional connectome” Brain Activity Map (BAM) would leverage current progress in neuroscience, synthetic biology, and nanotechnology to develop a map of each firing of every neuron in the human brain—a hundred billion neurons sampled on millisecond time scales. Although not the intended goal of this effort, a project on this scale, if it is funded, should also indirectly advance efforts to develop artificial intelligence and atomically precise manufacturing.

As Lewis notes in his posting, there’s an excellent description of BAM and other brain projects, as well as a discussion about how these ideas are linked (not necessarily by individuals but by the overall direction of work being done in many labs and in many countries across the globe) in Robert Blum’s Feb. (??), 2013 posting titled, BAM: Brain Activity Map Every Spike from Every Neuron, on his eponymous blog. Blum also offers an extensive set of links to the reports and stories about BAM. From Blum’s posting,

The essence of the BAM proposal is to create the technology over the coming decade
to be able to record every spike from every neuron in the brain of a behaving organism.
While this notion seems insanely ambitious, coming from a group of top investigators,
the paper deserves scrutiny. At minimum it shows what might be achieved in the future
by the combination of nanotechnology and neuroscience.

In 2013, as I write this, two European Flagship projects have just received funding for
one billion euro each (1.3 billion dollars each). The Human Brain Project is
an outgrowth of the Blue Brain Project, directed by Prof. Henry Markram
in Lausanne, which seeks to create a detailed simulation of the human brain.The Graphene Flagship, based in Sweden, will explore uses of graphene for,
among others, creation of nanotech-based supercomputers. The potential synergy
between these projects is a source of great optimism.

The goal of the BAM Project is to elaborate the functional connectome
of a live organism: that is, not only the static (axo-dendritic) connections
but how they function in real-time as thinking and action unfold.

…

The European Flagship Human Brain Project will create the computational
capability to simulate large, realistic neural networks. But to compare the model
with reality, a real-time, functional, brain-wide connectome must also be created.
Nanotech and neuroscience are mature enough to justify funding this proposal.

I highly recommend reading Blum’s technical description of neural spikes as understanding that concept or any other in his post doesn’t require an advanced degree. Note: Blum holds a number of degrees and diplomas including an MD (neuroscience) from the University of California at San Francisco and a PhD in computer science and biostatistics from California’s Stanford University.

The Human Brain Project has been mentioned here previously. The most recent mention is in a Jan. 28, 2013 posting about its newly gained status as one of two European Flagship initiatives (the other is the Graphene initiative) each meriting one billion euros of research funding over 10 years. Today, however, is the first time I’ve encountered the BAM project and I’m fascinated. Luckily, John Markoff’s Feb. 17, 2013 article for The New York Times provides some insight into this US initiative (Note: I have removed some links),

The Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, seeking to do for the brain what the Human Genome Project did for genetics.

The project, which the administration has been looking to unveil as early as March, will include federal agencies, private foundations and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

…

Moreover, the project holds the potential of paving the way for advances in artificial intelligence.

What I find particularly interesting is the reference back to the human genome project, which may explain why BAM is also referred to as a ‘connectome’.

ETA Mar.6.13: I have found a Human Connectome Project Mar. 6, 2013 news release on EurekAlert, which leaves me confused. This does not seem to be related to BAM, although the articles about BAM did reference a ‘connectome’. At this point, I’m guessing that BAM and the ‘Human Connectome Project’ are two related but different projects and the reference to a ‘connectome’ in the BAM material is meant generically. I previously mentioned the Human Connectome Project panel discussion held at the AAAS (American Association for the Advancement of Science) 2013 meeting in my Feb. 7, 2013 posting.

Its official title is the Montréal Neurological Institute and Hospital (Montréal Neuro) which is and has been, for several decades, an international centre for cutting edge neurological research. From the Jan. 28, 2013 news release on EurekAlert,

The Neuro

The Montreal Neurological Institute and Hospital — The Neuro, is a unique academic medical centre dedicated to neuroscience. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre.

Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, visit theneuro.com.

Nonetheless, it was a little surprising to see that ‘The Neuro’ is part one of the biggest research projects in history since it’s the European Union, which is bankrolling the project (see my posting about the Jan. 28, 2013 announcement of the winning FET Flagship Initatives). Here’s more information about the project, its lead researchers, and Canada’s role, from the news release,

The goal of the Human Brain Project is to pull together all our existing knowledge about the human brain and to reconstruct the brain, piece by piece, in supercomputer-based models and simulations. The models offer the prospect of a new understanding of the human brain and its diseases and of completely new computing and robotic technologies. On January 28 [2013], the European Commission supported this vision, announcing that it has selected the HBP as one of two projects to be funded through the new FET [Future and Emerging Technologies] Flagship Program.

Federating more than 80 European and international research institutions, the Human Brain Project is planned to last ten years (2013-2023). The cost is estimated at 1.19 billion euros. The project will also associate some important North American and Japanese partners. It will be coordinated at the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, by neuroscientist Henry Markram with co-directors Karlheinz Meier of Heidelberg University, Germany, and Richard Frackowiak of Centre Hospitalier Universitaire Vaudois (CHUV) and the University of Lausanne (UNIL).

Canada’s role in this international project is through Dr. Alan Evans of the Montreal Neurological Institute (MNI) at McGill University. His group has developed a high-performance computational platform for neuroscience (CBRAIN) and multi-site databasing technologies that will be used to assemble brain imaging data across the HBP. He is also collaborating with European scientists on the creation of ultra high-resolution 3D brain maps. «This ambitious project will integrate data across all scales, from molecules to whole-brain organization. It will have profound implications for our understanding of brain development in children and normal brain function, as well as for combatting brain disorders such as Alzheimer’s Disease,» said Dr. Evans. “The MNI’s pioneering work on brain imaging technology has led to significant advances in our understanding of the brain and neurological disorders,” says Dr. Guy Rouleau, Director of the MNI. “I am proud that our expertise is a key contributor to this international program focused on improving quality of life worldwide.”

“The Canadian Institutes of Health Research (CIHR) is delighted to acknowledge the outstanding contributions of Dr. Evans and his team. Their work on the CBRAIN infrastructure and this leading-edge HBP will allow the integration of Canadian neuroscientists into an eventual global brain project,” said Dr. Anthony Phillips, Scientific Director for the CIHR Institute of Neurosciences, Mental Health and Addiction. “Congratulations to the Canadian and European researchers who will be working collaboratively towards the same goal which is to provide insights into neuroscience that will ultimately improve people’s health.”

“From mapping the sensory and motor cortices of the brain to pioneering work on the mechanisms of memory, McGill University has long been synonymous with world-class neuroscience research,” says Dr. Rose Goldstein, Vice-Principal (Research and International Relations). “The research of Dr. Evans and his team marks an exciting new chapter in our collective pursuit to unlock the potential of the human brain and the entire nervous system – a critical step that would not be possible without the generous support of the European Commission and the FET Flagship Program.”

Canada is not the only non-European Union country making an announcement about its role in this extraordinary project. There’s a Jan. 28, 2013 news release on EurekAlert touting Israel’s role,

The European Commission has chosen the Human Brain Project, in which the Hebrew University of Jerusalem is participating, as one of two Future and Emerging Technologies Flagship topics. The enterprise will receive funding of 1.19 billion euros over the next decade.

The project will bring together top scientists from around the world who will work on one of the great challenges of modern science: understanding the human brain. Participating from Israel will a team of eight scientists, led by Prof. Idan Segev of the Edmond and Lily Safra Center for Brain Sciences (ELSC) at the Hebrew University, Prof. Yadin Dudai of the Weizmann Institute of Science, and Dr. Mira Marcus-Kalish of Tel Aviv University.

…

More than 80 universities and research institutions in Europe and the world will be involved in the ten-year Human Brain Project, which will commence later this year and operate until the year 2023. The project will be centered at the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland, headed by Prof. Henry Markram, a former Israeli who was recruited ten years ago to the EPFL.

The participation of the Israeli scientists testifies to the leading role that Israeli brain research occupies in the world, said Israeli President Shimon Peres. “Israel has put brain research at the heart of its efforts for the coming decade, and our country is already spearheading the global effort towards the betterment of our understanding of mankind. I am confident that the forthcoming discoveries will benefit a wide range of domains, from health to industry, as well as our society as a whole,” Peres said.

“The human brain is the most complex and amazing structure in the universe, yet we are very far from understanding it. In a way, we are strangers to ourselves. Unraveling the mysteries of the brain will help us understand our functioning, our choices, and ultimately ourselves. I congratulate the European Commission for its vision in selecting the Human Brain Project as a Flagship Mission for the forthcoming decade,” said Peres.

What’s amusing is that as various officials and interested parties (such as myself) wax lyrical about these projects, most of the rest of the world is serenely oblivious to it all.

Granted, we may not be able to lift a spaceship out of a swamp like Yoda does in The Empire Strikes Back, but it is possible to steer a model car, drive a wheelchair and control a robotic exoskeleton with just your thoughts.

…

We are standing in a testing room at IBM’s Emerging Technologies lab in Winchester, England.

On my head is a strange headset that looks like a black plastic squid. Its 14 tendrils, each capped with a moistened electrode, are supposed to detect specific brain signals.

In front of us is a computer screen, displaying an image of a floating cube.

As I think about pushing it, the cube responds by drifting into the distance.

Moskvitch goes on to discuss a number of projects that translate thought into movement via various pieces of equipment before she mentions a project at Brown University (US) where researchers are implanting computer chips into brains,

Headsets and helmets offer cheap, easy-to-use ways of tapping into the mind. But there are other,

Imagine some kind of a wireless computer device in your head that you’ll use for mind control – what if people hacked into that”

…

At Brown Institute for Brain Science in the US, scientists are busy inserting chips right into the human brain.

Subjects still have to be physically “plugged” into a computer via cables coming out of their heads, in a setup reminiscent of the film The Matrix. However, the team is now working on miniaturising the chips and making them wireless.

The purpose of the first phase of the pilot clinical study of the BrainGate2 Neural Interface System is to obtain preliminary device safety information and to demonstrate the feasibility of people with tetraplegia using the System to control a computer cursor and other assistive devices with their thoughts. Another goal of the study is to determine the participants’ ability to operate communication software, such as e-mail, simply by imagining the movement of their own hand. The study is invasive and requires surgery.

Individuals with limited or no ability to use both hands due to cervical spinal cord injury, brainstem stroke, muscular dystrophy, or amyotrophic lateral sclerosis (ALS) or other motor neuron diseases are being recruited into a clinical study at Massachusetts General Hospital (MGH) and Stanford University Medical Center. Clinical trial participants must live within a three-hour drive of Boston, MA or Palo Alto, CA. Clinical trial sites at other locations may be opened in the future. The study requires a commitment of 13 months.

They have been recruiting since at least November 2011, from the Nov. 14, 2011 news item by Tanya Lewis on MedicalXpress,

Stanford University researchers are enrolling participants in a pioneering study investigating the feasibility of people with paralysis using a technology that interfaces directly with the brain to control computer cursors, robotic arms and other assistive devices.

…

The pilot clinical trial, known as BrainGate2, is based on technology developed at Brown University and is led by researchers at Massachusetts General Hospital, Brown and the Providence Veterans Affairs Medical Center. The researchers have now invited the Stanford team to establish the only trial site outside of New England.

Under development since 2002, BrainGate is a combination of hardware and software that directly senses electrical signals in the brain that control movement. The device — a baby-aspirin-sized array of electrodes — is implanted in the cerebral cortex (the outer layer of the brain) and records its signals; computer algorithms then translate the signals into digital instructions that may allow people with paralysis to control external devices.

Confusingly, there seemto be two BrainGate organizations. One appears to be a research entity where a number of institutions collaborate and the other is some sort of jointly held company. From the About Us webpage of the BrainGate research entity,

In the late 1990s, the initial translation of fundamental neuroengineering research from “bench to bedside” – that is, to pilot clinical testing – would require a level of financial commitment ($10s of millions) available only from private sources. In 2002, a Brown University spin-off/startup medical device company, Cyberkinetics, Inc. (later, Cyberkinetics Neurotechnology Systems, Inc.) was formed to collect the regulatory permissions and financial resources required to launch pilot clinical trials of a first-generation neural interface system. The company’s efforts and substantial initial capital investment led to the translation of the preclinical research at Brown University to an initial human device, the BrainGate Neural Interface System [Caution: Investigational Device. Limited by Federal Law to Investigational Use]. The BrainGate system uses a brain-implantable sensor to detect neural signals that are then decoded to provide control signals for assistive technologies. In 2004, Cyberkinetics received from the U.S. Food and Drug Administration (FDA) the first of two Investigational Device Exemptions (IDEs) to perform this research. Hospitals in Rhode Island, Massachusetts, and Illinois were established as clinical sites for the pilot clinical trial run by Cyberkinetics. Four trial participants with tetraplegia (decreased ability to use the arms and legs) were enrolled in the study and further helped to develop the BrainGate device. Initial results from these trials have been published or presented, with additional publications in preparation.

While scientific progress towards the creation of this promising technology has been steady and encouraging, Cyberkinetics’ financial sponsorship of the BrainGate research – without which the research could not have been started – began to wane. In 2007, in response to business pressures and changes in the capital markets, Cyberkinetics turned its focus to other medical devices. Although Cyberkinetics’ own funds became unavailable for BrainGate research, the research continued through grants and subcontracts from federal sources. By early 2008 it became clear that Cyberkinetics would eventually need to withdraw completely from directing the pilot clinical trials of the BrainGate device. Also in 2008, Cyberkinetics spun off its device manufacturing to new ownership, BlackRock Microsystems, Inc., which now produces and is further developing research products as well as clinically-validated (510(k)-cleared) implantable neural recording devices.

Beginning in mid 2008, with the agreement of Cyberkinetics, a new, fully academically-based IDE application (for the “BrainGate2 Neural Interface System”) was developed to continue this important research. In May 2009, the FDA provided a new IDE for the BrainGate2 pilot clinical trial. [Caution: Investigational Device. Limited by Federal Law to Investigational Use.] The BrainGate2 pilot clinical trial is directed by faculty in the Department of Neurology at Massachusetts General Hospital, a teaching affiliate of Harvard Medical School; the research is performed in close scientific collaboration with Brown University’s Department of Neuroscience, School of Engineering, and Brown Institute for Brain Sciences, and the Rehabilitation Research and Development Service of the U.S. Department of Veteran’s Affairs at the Providence VA Medical Center. Additionally, in late 2011, Stanford University joined the BrainGate Research Team as a clinical site and is currently enrolling participants in the clinical trial. This interdisciplinary research team includes scientific partners from the Functional Electrical Stimulation Center at Case Western Reserve University and the Cleveland VA Medical Center. As was true of the decades of fundamental, preclinical research that provided the basis for the recent clinical studies, funding for BrainGate research is now entirely from federal and philanthropic sources.

The BrainGate Research Team at Brown University, Massachusetts General Hospital, Stanford University, and Providence VA Medical Center comprises physicians, scientists, and engineers working together to advance understanding of human brain function and to develop neurotechnologies for people with neurologic disease, injury, or limb loss.

The BrainGate™ Co. is a privately-held firm focused on the advancement of the BrainGate™ Neural Interface System. The Company owns the Intellectual property of the BrainGate™ system as well as new technology being developed by the BrainGate company. In addition, the Company also owns the intellectual property of Cyberkinetics which it purchased in April 2009.

Meanwhile, in Europe there are two projects BrainAble and the Human Brain Project. The BrainAble project is similar to BrainGate in that it is intended for people with injuries but they seem to be concentrating on a helmet or cap for thought transmission (as per Moskovitch’s experience at the beginning of this posting). From the Feb. 28, 2012 news item on Science Daily,

In the 2009 film Surrogates, humans live vicariously through robots while safely remaining in their own homes. That sci-fi future is still a long way off, but recent advances in technology, supported by EU funding, are bringing this technology a step closer to reality in order to give disabled people more autonomy and independence than ever before.

…

“Our aim is to give people with motor disabilities as much autonomy as technology currently allows and in turn greatly improve their quality of life,” says Felip Miralles at Barcelona Digital Technology Centre, a Spanish ICT research centre.

Mr. Miralles is coordinating the BrainAble* project (http://www.brainable.org/), a three-year initiative supported by EUR 2.3 million in funding from the European Commission to develop and integrate a range of different technologies, services and applications into a commercial system for people with motor disabilities.

In terms of HCI [human-computer interface], BrainAble improves both direct and indirect interaction between the user and his smart home. Direct control is upgraded by creating tools that allow controlling inner and outer environments using a “hybrid” Brain Computer Interface (BNCI) systemable to take into account other sources of information such as measures of boredom, confusion, frustration by means of the so-called physiological and affective sensors.

Furthermore, interaction is enhanced by means of Ambient Intelligence (AmI) focused on creating a proactive and context-aware environments by adding intelligence to the user’s surroundings. AmI’s main purpose is to aid and facilitate the user’s living conditions by creating proactive environments to provide assistance.

Human-Computer Interfaces are complemented by an intelligent Virtual Reality-based user interface with avatars and scenarios that will help the disabled move around freely, and interact with any sort of devices. Even more the VR will provide self-expression assets using music, pictures and text, communicate online and offline with other people, play games to counteract cognitive decline, and get trained in new functionalities and tasks.

Perhaps this video helps,

Another European project, NeuroCare, which I discussed in my March 5, 2012 posting, is focused on creating neural implants to replace damaged and/or destroyed sensory cells in the eye or the ear.

The Human Brain Project is, despite its title, a neuromorphic engineering project (although the researchers do mention some medical applications on the project’s home page) in common with the work being done at the University of Michigan/HRL Labs mentioned in my April 19, 2012 posting (A step closer to artificial synapses courtesy of memritors) about that project. From the April 11, 2012 news item about the Human Brain Project on Science Daily,

Researchers at the EPFL [Ecole Polytechnique Fédérale de Lausanne] have discovered rules that relate the genes that a neuron switches on and off, to the shape of that neuron, its electrical properties and its location in the brain.

The discovery, using state-of-the-art informatics tools, increases the likelihood that it will be possible to predict much of the fundamental structure and function of the brain without having to measure every aspect of it. That in turn makes the Holy Grail of modelling the brain in silico — the goal of the proposed Human Brain Project — a more realistic, less Herculean, prospect. “It is the door that opens to a world of predictive biology,” says Henry Markram, the senior author on the study, which is published this week in PLoS ONE.

Today, simulating a single neuron requires the full power of a laptop computer. But the brain has billions of neurons and simulating all them simultaneously is a huge challenge. To get round this problem, the project will develop novel techniques of multi-level simulation in which only groups of neurons that are highly active are simulated in detail. But even in this way, simulating the complete human brain will require a computer a thousand times more powerful than the most powerful machine available today. This means that some of the key players in the Human Brain Project will be specialists in supercomputing. Their task: to work with industry to provide the project with the computing power it will need at each stage of its work.

The Human Brain Project will impact many different areas of society. Brain simulation will provide new insights into the basic causes of neurological diseases such as autism, depression, Parkinson’s, and Alzheimer’s. It will give us new ways of testing drugs and understanding the way they work. It will provide a test platform for new drugs that directly target the causes of disease and that have fewer side effects than current treatments. It will allow us to design prosthetic devices to help people with disabilities. The benefits are potentially huge. As world populations grow older, more than a third will be affected by some kind of brain disease. Brain simulation provides us with a powerful new strategy to tackle the problem.

The project also promises to become a source of new Information Technologies. Unlike the computers of today, the brain has the ability to repair itself, to take decisions, to learn, and to think creatively – all while consuming no more energy than an electric light bulb. The Human Brain Project will bring these capabilities to a new generation of neuromorphic computing devices, with circuitry directly derived from the circuitry of the brain. The new devices will help us to build a new generation of genuinely intelligent robots to help us at work and in our daily lives.

The Human Brain Project builds on the work of the Blue Brain Project. Led by Henry Markram of the Ecole Polytechnique Fédérale de Lausanne (EPFL), the Blue Brain Project has already taken an essential first towards simulation of the complete brain. Over the last six years, the project has developed a prototype facility with the tools, know-how and supercomputing technology necessary to build brain models, potentially of any species at any stage in its development. As a proof of concept, the project has successfully built the first ever, detailed model of the neocortical column, one of the brain’s basic building blocks.

The Human Brain Project is a flagship project in contention for the 1B Euro research prize that I’ve mentioned in the context of the GRAPHENE-CA flagship project (my Feb. 13, 2012 posting gives a better description of these flagship projects while mentioned both GRAPHENE-CA and another brain-computer interface project, PRESENCCIA).

Part of the reason for doing this roundup, is the opportunity to look at a number of these projects in one posting; the effect is more overwhelming than I expected.

I do have earlier postings on brains and neuroprostheses, one of the more recent ones is this March 16, 2012 posting. Meanwhile, there are new announcements from Northwestern University (US) and the US National Institutes of Health (National Institute of Neurological Disorders and Stroke). From the April 18, 2012 news item (originating from the National Institutes of Health) on Science Daily,

An artificial connection between the brain and muscles can restore complex hand movements in monkeys following paralysis, according to a study funded by the National Institutes of Health.

In a report in the journal Nature, researchers describe how they combined two pieces of technology to create a neuroprosthesis — a device that replaces lost or impaired nervous system function. One piece is a multi-electrode array implanted directly into the brain which serves as a brain-computer interface (BCI). The array allows researchers to detect the activity of about 100 brain cells and decipher the signals that generate arm and hand movements. The second piece is a functional electrical stimulation (FES) device that delivers electrical current to the paralyzed muscles, causing them to contract. The brain array activates the FES device directly, bypassing the spinal cord to allow intentional, brain-controlled muscle contractions and restore movement.

A new Northwestern Medicine brain-machine technology delivers messages from the brain directly to the muscles — bypassing the spinal cord — to enable voluntary and complex movement of a paralyzed hand. The device could eventually be tested on, and perhaps aid, paralyzed patients.

…

The research was done in monkeys, whose electrical brain and muscle signals were recorded by implanted electrodes when they grasped a ball, lifted it and released it into a small tube. Those recordings allowed the researchers to develop an algorithm or “decoder” that enabled them to process the brain signals and predict the patterns of muscle activity when the monkeys wanted to move the ball.

These experiments were performed by Christian Ethier, a post-doctoral fellow, and Emily Oby, a graduate student in neuroscience, both at the Feinberg School of Medicine. The researchers gave the monkeys a local anesthetic to block nerve activity at the elbow, causing temporary, painless paralysis of the hand. With the help of the special devices in the brain and the arm — together called a neuroprosthesis — the monkeys’ brain signals were used to control tiny electric currents delivered in less than 40 milliseconds to their muscles, causing them to contract, and allowing the monkeys to pick up the ball and complete the task nearly as well as they did before.

“The monkey won’t use his hand perfectly, but there is a process of motor learning that we think is very similar to the process you go through when you learn to use a new computer mouse or a different tennis racquet. Things are different and you learn to adjust to them,” said Miller [Lee E. Miller], also a professor of physiology and of physical medicine and rehabilitation at Feinberg and a Sensory Motor Performance Program lab chief at the Rehabilitation Institute of Chicago.

The National Institutes of Health news item supplies a little history and background for this latest breakthrough while the Northwestern University news item offers more technical details more technical details.

You can find the researchers’ paper with this citation (assuming you can get past the paywall,